Increases in glomerular cellularity and accumulation of extracellular matrix material and are prominent histologic findings in a number of clinical and experimental glomerular diseases. Transforming growth factor-beta (TGF-beta) has been identified as a potentially important modulator of glomerular pathology based on its demonstrated ability to regulate proliferation and extracellular matrix synthesis by cultured glomerular cells. The goal of these studies is to better understand the expression, actions, and mechanisms of action of TGF-beta on glomeruli in vivo. We found that normal rat glomeruli contain high concentrations of TGF-beta- l, TGF-beta-2 and their corresponding mRNAs. We also found that a marked disparity exists between the TGF-beta receptor phenotype identified on cultured glomerular cells and the TGF-beta binding proteins or receptors which are present in intact glomeruli. Cultured glomerular cells express typical type I and II TGF-beta receptors. These receptors are not evident in intact glomeruli. Instead, glomeruli contain a unique group of disulfide linked TGF-beta binding proteins which bind TGF-beta1 but not TGF-beta2. These results suggest that glomeruli may respond quite differently than cultured cells do to TGF-beta. This could be due to preexisting maximal stimulation of glomerular cells by endogenous TGF-beta, absence of typical cellular receptors for TGF-beta, or to modulation of response by the TGF-beta1 selective binding proteins.